Infection of the fetus with cytomegalovirus (CMV) results in approximately 8,000 infants born each year who will be mentally retarded and/or deaf. These effects are mainly due to primary maternal CMV infections in daycare and shed the virus for between 3 and 41 months (mean of 18 months). At least half of seronegative mothers with infected children under age 2 years acquire CMV from their children within one year compared to an annual rate of <5 percent among other seronegative women. Adolescents also have a high rate of CMV infection during pregnancy and high rates of congenital infection. CMV vaccines with the potential to control this infection are available for evaluation. An effective national vaccination strategy to prevent primary maternal infection during pregnancy should include immunization before pregnancy. In adults we found that natural seropositivity protects against reinfections. To determine the feasibility of immunizing mothers against CMV we will compare immunity and protection induced by two CMV vaccines, a live attenuated strain, Towne, and a purified protein vaccine, CMV gB/MF59, in an expanded placebo controlled double blinded efficacy trial. Because subjects in this study will have a high rate of primary CMV infections we will be testing the hypothesis that subjects will be protected against infection and protection will be associated with high levels of neutralizing antibodies. We will compare the infection rate as measured serologically and viral shedding and the rate of CMV DNAemia of 120 women to the infection rate of 120 matched seronegative women immunized with Towne vaccine and 120 women immunized with CMV gB/MF59 vaccine. We will also determine if infection is associated with a subject's immune response. The parameters of the immune response to be measured will include IgG, IgG to CMV gB, neutralizing titers, IgG responses characterized by immunoblotting, CD4+ responder cell frequencies, cytotoxic T cells (CD8+) and mucosal immunity. The results of this study will establish if immunization of mothers against CMV infection is possible.